Minoxidil (i.e., 2,4-diamino-6-piperidinylpyrimidine-3-oxide) is the active ingredient of Loniten® and Rogaine®, which are marketed by Pharmacia & Upjohn as a treatment for hypertension, and as a treatment and preventative for androgenic alopecia (male and female pattern baldness), respectively. The preparation and antihypertensive use of minoxidil is described in U.S. Pat. No. 3,461,461. Methods and topical preparations for using the compound to grow hair and to treat male and female pattern baldness are described and claimed in U.S. Pat. Nos. 4,139,619 and 4,596,812.
Pharmaceutical compositions for topical application, such as Rogaine®, may take a variety of forms including, for example, solutions, gels, suspensions, and the like. Generally speaking, improved absorption may be achieved when the topical compositions are in the form of a solution or gel, i.e., where the active ingredient, for example, minoxidil, is dissolved in the carrier solution, in contrast to topical compositions which are in the form of suspensions, i.e., where the active ingredient is merely suspended in the composition.
Solutions of minoxidil typically contain water and one or more additional solvents. Topical solutions have not been entirely satisfactory for use in treating the scalp, however, as they tend not to remain in place long enough for satisfactory amounts of the drug to be absorbed. Formulations of minoxidil, such as jellies and ointments, have also been proposed. These compositions may not be pharmaceutically elegant, and also may not be suitable for use as treatments for stimulating the growth of hair, especially from a cosmetic point of view.
The use of polymeric thickening agents as part of the delivery vehicle for minoxidil, has also been described. GB 2 194 887, for example, describes a preparation containing a polymer, up to 20% solvent (i.e. propylene glycol), and up to 5% minoxidil. This application teaches that at least a part of the minoxidil may be in the form of micronized particles suspended in the delivery medium, however, rather than in solution. U.S. Pat. No. 5,225,189 also describes preparations containing a carbomeric polymer, and provides examples of single-phase gel preparations having up to 3% solubilized minoxidil therein.
Attempts to provide pharmaceutically appropriate thickened formulations containing higher concentrations of solubilized minoxidil are hampered, however, by various processing difficulties. For example, minoxidil is poorly soluble, and may precipitate out of solution by the addition of additional ingredients, such as thickening agents. Accordingly, high percentages of solvents, such as propylene glycol and alcohol, may be required. Frequently, however, these high solvent percentages may be incompatible with many pharmaceutical additives, such as thickening agents, and may generally result in a pharmaceutically inelegant product. Carbopol® 934P, for example, the carbomer polymer used in the examples of U.S. Pat. No. 5,225,189, in the presence of high percentages of solvent and inadequate amounts of water, affords a thick, doughy mass that may be unworkable with equipment commonly employed to manufacture pharmaceutical products.
There remains a need for new pharmaceutically elegant compositions of minoxidil which can be prepared using the equipment and techniques commonly used for the large scale, commercial production of topical pharmaceutical preparations. The present invention is directed to these, as well as other, important ends.